Gluconeogenesis and PPP

C483 Spring 2013

1. An intermediate found in gluconeogenesis and not glycolysis isA) 2-phosphoglycerate.B) oxaloacetate.C) phosphoenolpyruvate.D) fructose 1,6-bisphosphate.

2. In the Cori Cycle, _____ is transported through blood to the liver, where it is made into ________ and then ___________ for transport out of the liver.A) glucose, lactate, pyruvateB) Pyruvate, lactate, glucoseC) Lactate, glucose, pyruvateD) Pyruvate, glucose, lactateE) Lactate, pyruvate, glucose

3. Gluconeogenesis is regulated by A) glucagon.B) allosteric modulation.C) concentration of its substrates.D) All of the above.

4. Which statement is false: The three points of difference between glycolysis and gluconeogenesis are necessaryA) To allow for reciprocal regulation of the pathwaysB) To make each pathway energetically downhillC) So that glucose can be simultaneously made and used in the same cellD) To catalyze reactions unique to each pathway

5. The major purpose of the PPP is _____________, and the secondary purpose is __________.E) NADPH production; regeneration of C6 carbohydrates.F) NAD+ recycling; formation of C5 carbohydrates.G) Synthesis of NADPH; synthesis of C5 carbohydratesH) Synthesis of C5 carbohydrates; synthesis of reducing powerI) Oxidative stage; non-oxidative stage

Glucose Metabolism Overview

• Keep the main pathway purposes distinct

• But learn details of chemistry and regulation based on similarities

OHO

HO

OH (P)

OH

OH

DHAP

Pyruvate

Gluconeogenesis

Lactate

Amino Acids

Glycerol(Triacylglycerides)

Glycogen

Glycogen Degradation

Glycogen

Glycogen Synthesis

Ribose,NADPH

ATP

DHAP

Pyruvate

Pentose Phosphate Pathway

Energy Production

Starch

Diet

Precursors for Gluconeogenesis

• Names of compounds?

• Type of reaction?• Type of enzyme?• Cofactor(s)?• More on lactate

processing…

OH

OH

OH

OPO3

O

OH

O

O

O

NH2

O

O

O

O

O

OH

O

O

Cori Cycle• Inter-tissue

metabolism• Don’t waste the

lactate made in muscle!– Transport to live– Convert to pyruvate

then glucose– Store glucose

• Which can be sent back to muscle

Chemistry of Gluconeogenesis

• Chemically opposite of glycolysis (mainly)• Energetically costly—no perpetual motion

machine!• Points of regulation

Glycolysis• Step 1: costs 1 ATP• Step 3: costs 1 ATP• Step 7: makes 2 ATP• Step 10: makes 2

ATP

• Gluconeogenesis• Step 10: no change• Step 8: no change• Step 3: costs 2 ATP• Step 1: costs 4 ATP

equivalents

Step 1

• Pyruvate Carboxylase– Biotin– ATP cost to make

driving force for next reaction

• PEP carboxykinase– ATP cost to restore

PEP– CO2 loss drives rxn

Step 8• Fructose-1,6-bisphosphatase• No additional energy input• Phosphate ester hydrolysis is spontaneous

Step 10

• Glucose 6-phosphatase– Liver (and others)– Not in muscle

Regulation• Principle of

Reciprocal regulation– AMP– Citrate/Acetyl CoA– Frutose-2,6-

bisphosphate

Key Regulation

• Reciprical Regulation of PFK-1 and fructose-1,6-bisphosphatase– Energy waste at committed step– Hormone regulated

Glucose Metabolism Overview

• Gluconeogenesis• Pentose

Phosphate Pathway

• Glycogen metabolism

OHO

HO

OH (P)

OH

OH

DHAP

Pyruvate

Gluconeogenesis

Lactate

Amino Acids

Glycerol(Triacylglycerides)

Glycogen

Glycogen Degradation

Glycogen

Glycogen Synthesis

Ribose,NADPH

ATP

DHAP

Pyruvate

Pentose Phosphate Pathway

Energy Production

Pentose Phosphate Pathway

• Dual Purpose– Synthesis of “reducing potential”– Synthesis of 5-carbon sugars

• Net reaction

Complex, 2-Stage Process

• No details except glucose-6-P DH

• No reactions!• Just overall

purposes– Oxidative Stage– Non-oxidative

stage

Non-oxidative Stage

• To understand purpose, realize that we generally need to make much more NADPH than ribose

• Problem: stuck with C5, but need C6 and C3

• Solution: “Shunt” C5 back to C6 through near-equilibrium reactions

Answers

1. B2. E3. D4. C5. C